The syndromic approach to diagnosis requires as homogeneous a clinical population as possible. We will achieve this by excluding patients with active psychiatric problems occurring in the 5 years prior to onset of CFS. Remaining patients plus age and sex matched controls will be evaluated virologically and immunologically in Projects 2 and 3 in Study 1 of this Project. Based on classifications derived from that testing, patients will undergo additional testing aimed at understanding many of their CFS symptoms. These include problems with attention and memory, unstable body temperature, fatigue and weakness especially after a period of exertion, and symptoms referent to the autonomic nervous system such as lightheadedness, dizziness and palpitation. Our working hypothesis is that CFS patients with abnormal viral-immunological testing will have other identifiable abnormalities which would help to understand their symptoms. And CFS patients who test normally will probably resemble either our normal or depressed control populations. Study 2 seeks to untie the knot between organicity, depression and fatigue by neuropsychological testing of the CFS patient, the depressed outpatient prior to medication, and the patient with mild MS -- an illness which produces central fatigue. Study 3 will assess body temperature by ambulatory monitoring in patients and controls. Study 4 will evaluate muscle metabolism and biochemical kinetics in CFS patients prior to, during and after submaximal exercise; this study will be done on a day when muscle symptoms are mild and on a day following exercise when they are marked. Study 5 looks at the metabolic and autonomic consequences of exercise-induced fatigue during and after ambulation on a treadmill. And Study 6 evaluates the hypothesis that many of the patients' symptoms are due to stress-related chronic hyperventilation. These studies provide an integrated and rigorous scientific approach to the problem and CFS. Their outcome will allow the Center to organize a standardized way to assess new patients with CFS for diagnostic purposes so that treatment regimens appropriate to the diagnosis can be developed.